University of Milano-Bicocca

About: University of Milano-Bicocca is a education organization based out in Milan, Italy. It is known for research contribution in the topics: Population & Blood pressure. The organization has 8972 authors who have published 22322 publications receiving 620484 citations. The organization is also known as: Università degli Studi di Milano-Bicocca & Universita degli Studi di Milano-Bicocca.

Proton pump inhibition induces autophagy as a survival mechanism following oxidative stress in human melanoma cells

Abstract: Proton pump inhibitors (PPI) target tumour acidic pH and have an antineoplastic effect in melanoma. The PPI esomeprazole (ESOM) kills melanoma cells through a caspase-dependent pathway involving cytosolic acidification and alkalinization of tumour pH. In this paper, we further investigated the mechanisms of ESOM-induced cell death in melanoma. ESOM rapidly induced accumulation of reactive oxygen species (ROS) through mitochondrial dysfunctions and involvement of NADPH oxidase. The ROS scavenger N-acetyl-L-cysteine (NAC) and inhibition of NADPH oxidase significantly reduced ESOM-induced cell death, consistent with inhibition of cytosolic acidification. Autophagy, a cellular catabolic pathway leading to lysosomal degradation and recycling of proteins and organelles, represents a defence mechanism in cancer cells under metabolic stress. ESOM induced the early accumulation of autophagosomes, at the same time reducing the autophagic flux, as observed by WB analysis of LC3-II accumulation and by fluorescence microscopy. Moreover, ESOM treatment decreased mammalian target of rapamycin signalling, as reduced phosphorylation of p70-S6K and 4-EBP1 was observed. Inhibition of autophagy by knockdown of Atg5 and Beclin-1 expression significantly increased ESOM cytotoxicity, suggesting a protective role for autophagy in ESOM-treated cells. The data presented suggest that autophagy represents an adaptive survival mechanism to overcome drug-induced cellular stress and cytotoxicity, including alteration of pH homeostasis mediated by proton pump inhibition.

A distinctive example of the cooperative interplay of structure and environment in tuning of intramolecular charge transfer in second-order nonlinear optical chromophores.

Abstract: The strongly enhanced coop- erative influence of medium polarity and organic structural design on the first hyperpolarizability of a novel family of highly polarizable azinium-(CHCH- thienyl)-dicyanomethanido chromo- phores 1 ± 3 is described. The dyes can be efficiently synthesized by regioselec- tive protonation/alkylation of the corre- sponding bidentate anion precursors. Consecutive annelation of the pyridyl ring of 1 (pyridine quinoline acri- dine) and medium polarity effects are responsible for an extraordinarily varia- ble range of intramolecular charge transfer (ICT), leading to a large set of -electron distribution patterns. Ac- cordingly, systems with remarkably dif- ferent zwitterionic/quinoid character in the ground and excited states present values in a broad range, eventually switching from negative to positive. Our investigation is based on a combi- nation of experimental (UV/Vis spec- troscopy, multinuclear NMR spectrosco- py, and electrooptical absorption meas- urements) and computational (ab initio) approaches. It is shown that: 1) and are dramatically influenced, even by orders of magnitude, by a complex, non-monotonic interplay of structure and medium action, which in turn affects molecular ICT and bond length alterna- tion (BLA), 2) the computations, vali- dated by different experimental data, are to be recommended as an extremely useful tool in the search for a greatly improved set of molecular nonlinear optical (NLO) responses (in the case of 1 ± 3 they show that such conditions may be attained only in a narrow and limited range of dielectric constants in which the annelation effect operates most effi- ciently), and 3) the search for the most favorable molecular NLO response of a highly polarizable chromophore both in solution and in solid matrices should simultaneously take into account not only the molecular design supplemented by annelation effects but also the polar- ity of the medium.

Left ventricular hypertrophy increases cardiovascular risk independently of in-office and out-of-office blood pressure values.

Abstract: ObjectivesPrevious studies have shown that left ventricular hypertrophy (LVH) represents a cardiovascular risk factor independently of clinic blood pressure (BP). The present study was aimed at determining the impact of LVH on the incidence of cardiovascular morbid and fatal events taking into accou

Sudden death and associated factors in a historical cohort of chronic haemodialysis patients

Abstract: Background In haemodialysis patients, deaths due to cardiovascular causes constitute a large proportion of total mortality and sudden cardiac deaths account for approximately 22% of all deaths. The aim of this study was to evaluate the incidence of sudden cardiac death and associated risk factors in a cohort of haemodialysis patients. Methods and results The 3-year cumulative incidence of death in a cohort of 476 patients on chronic haemodialysis treatment was 34.3% (SE 2.3). Sudden death had a 6.9% (SE 1.2) cumulative incidence, with 32 events representing 19.2% of all deaths, while cardiovascular not sudden death and noncardiovascular death accounted for a 3-year cumulative incidence of 7.3% (SE 1.2) and 20.1% (SE 1.9), respectively. According to Cox multivariate analysis, significant risk factors for sudden death were the presence of atrial fibrillation, diabetes mellitus, predialytic hyperkalaemia, haemodialysis mode and C-reactive protein level, which were associated with a 2.9 (CI(95%) 1.3-6.4), 3.0 (CI(95%) 1.3-7.2), 2.7 (CI(95%) 1.3-5.8), 4.5 (CI(95%) 1.3-15.5) and 3.3 (CI(95%) 1.2-8.8)-fold increase in the risk of sudden death, respectively. Sudden death was significantly more frequent during the first 24 h of the first short interdialytic interval and during the last 24 h of the long interval, i.e. immediately before and immediately after the first weekly haemodialysis session (P = 0.02). Conclusions Our data show that the incidence of sudden death in haemodialysis patients is high and that atrial fibrillation, diabetes, hyperkalaemia, haemodialysis mode and C-reactive protein play an important role in developing fatal arrhythmia. Further studies will be necessary to define which interventions could be helpful in reducing this cause of mortality.